1. Field of the Invention
The present invention pertains to microfluidic devices and particle adhesion in biological microcirculation. In particular, the invention is a method for characterizing particle adhesion properties in idealized synthetic microvascular bifurcations and junctions and to predict particle adhesion dynamics in biological microcirculation.
2. Description of Related Art
A considerable body of work has been developed regarding in-vitro systems for the study of vascular endothelial responses, leukocyte adhesion, and drug carrier delivery in the microcirculation of capillary beds. For example, in-vitro flow chambers have facilitated the identification of biological molecules involved in the adhesion of leukocytes to the endothelium. These results have led in part to an effort to understand endothelial cell-leukocyte interactions using carefully controlled in-vitro flow cell experiments.
The adhesion of particles such as leukocytes, platelets, liposomes/lipisomes, and microencapsulated drug carriers to microvascular endothelium is influenced by the geometric features of the vasculature, local hemodynamics, and numerous receptor-ligand interactions between endothelial cells and particles. Local hemodynamic factors associated with microvascular geometry such as wall shear stress, pressure, and residence time influence the rates, amounts, and distributions of particle adhesion as well as endothelial cell morphology and function. This complex interplay between flow, cells, and particles is still poorly understood and it is not possible to predict, for example, adhesion patterns and numbers of adhered particles in the microvasculature based on current in-vitro flow cell technologies.
The present invention is based, in part, on the finding by the inventors that microfluidic surfaces at bifurcations and junctions in biological and synthetic microvascular networks interact with particles moving through them to an unexpected degree. The inventors have found that interactions of particles at synthetic bifurcations are predictive of and correlate with particle interactions in physiological bifurcations. This surprising finding indicates that simple, idealized bifurcations, junctions, and combinations thereof, fabricated using known technologies can be used, for example, to screen for particle and cell adhesion at corresponding structures in biological microvascular networks. Methods of the present invention can be used to screen particles and cells for the presence of desired or absence of undesirable interactions with the surfaces of biological microvascular structures such as bifurcations and junctions.